Intestine-Decipher Engineered Capsules Protect Against Sepsis-induced Intestinal Injury via Broad-spectrum Anti-inflammation and Parthanatos Inhibition.
Summary
An oral, pH-responsive capsule delivering macrophage membrane-coated olaparib nanoparticles targets injured intestine in sepsis, neutralizes cytokines, inhibits PARP1-driven parthanatos, reduces bacterial translocation, and improves survival in mice.
Key Findings
- Macrophage membrane-coated olaparib nanoparticles (OLA@MΦ NPs) in pH-responsive capsules resist gastric acid and release in the intestine, targeting injured tissue.
- Released nanoparticles neutralize pro-inflammatory cytokines via macrophage membrane receptors and inhibit PARP1-mediated parthanatos in intestinal epithelium.
- In septic mice, the therapy reduces bacterial translocation, attenuates sepsis progression, and improves survival.
Clinical Implications
If translatable, intestine-targeted, macrophage-mimetic nanoparticles could complement standard care by protecting the gut barrier and modulating hyperinflammation in sepsis.
Why It Matters
Introduces a dual-function, host-directed oral nanotherapy that addresses intestinal barrier failure—a central driver of sepsis progression—with survival benefits in vivo.
Limitations
- Preclinical murine study; human safety, dosing, and manufacturability remain untested
- Potential off-target immunomodulation and long-term effects of PARP inhibition in the gut are unknown
Future Directions
Evaluate pharmacokinetics, safety, and efficacy in large animals; optimize capsule release profiles; and investigate combinatorial regimens with standard sepsis care.
Study Information
- Study Type
- Basic/Mechanistic research
- Research Domain
- Treatment
- Evidence Level
- V - Preclinical therapeutic study in murine sepsis models
- Study Design
- OTHER